Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study

Br J Haematol. 2010 Jul;150(2):179-88. doi: 10.1111/j.1365-2141.2010.08212.x. Epub 2010 Apr 30.


Fanconi anaemia (FA), dyskeratosis congenita (DC), Diamond-Blackfan anaemia (DBA), and Shwachman-Diamond syndrome (SDS) comprise major inherited bone marrow failure syndromes (IBMFS). Adverse events include severe bone marrow failure (BMF), myelodysplastic syndrome (MDS), acute myeloid leukaemia (AML), and solid tumours (ST). The natural history of FA is well characterised; hazard rates in the other syndromes have not yet been quantified. An open cohort was established at the National Cancer Institute (NCI) in 2002. Patients enrolled prior to December, 2007 were followed up to December, 2008. Diagnoses were confirmed with standard tests. Age-associated risks of adverse events were calculated. Most patients in each syndrome survived to young adulthood. Patients with FA had earlier onset of cancers, need for stem cell transplant, and death; followed by DC; DBA and SDS were mildest. While FA and DC patients had markedly increased risks of cancer, AML and MDS, there were no cases of leukaemia in DBA or SDS patients. The NCI cohort provides the first direct quantitative comparison of timing and magnitude of cancer risk in the IBMFS. The findings demonstrate that both FA and DC are major cancer susceptibility syndromes. The IBMFS, historically considered paediatric disorders, have important management implications for physicians treating adult patients.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Anemia, Diamond-Blackfan / complications
  • Anemia, Diamond-Blackfan / genetics
  • Bone Marrow Diseases / complications*
  • Bone Marrow Diseases / genetics
  • Child
  • Child, Preschool
  • Dyskeratosis Congenita / complications
  • Dyskeratosis Congenita / genetics
  • Epidemiologic Methods
  • Fanconi Anemia / complications
  • Fanconi Anemia / genetics
  • Female
  • Genetic Diseases, Inborn / complications*
  • Genetic Diseases, Inborn / genetics
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Male
  • Middle Aged
  • Neoplasms / etiology*
  • Neoplasms / genetics
  • Prognosis
  • Syndrome
  • Young Adult